纳米碳酸钾脱除Fmoc保护基的新方法  

Novel deprotection method of Fmoc group using nano-K_2CO_3

作　　者：范士明 刘润娇 赵园 李朔 李星驰[2] 王鹏 刘守信 FAN Shiming;LIU Runjiao;ZHAO Yuan;LI Shuo;LI Xingchi;WANG Peng;LIU Shouxin(State Key Laboratory of Hebei Province Molecular Chemistry for Drug,Hebei University of Science and Technology,Shijiazhuang,Hebei 050018,China;School of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang,Hebei 050018,China)

机构地区：[1]河北省药用分子化学重点实验室,河北石家庄050018 [2]河北科技大学化学与制药工程学院,河北石家庄050018

出　　处：《河北科技大学学报》2018年第3期243-248,共6页Journal of Hebei University of Science and Technology

基　　金：河北省高等学校青年拔尖人才计划项目(BJ2017059);河北省高等学校科学技术研究青年基金(QN2017065);河北省食品药品监督管理局科技计划项目(QN2015017);河北省科技计划项目(16273812);河北省自然科学基金(B2015208134)

摘　　要：Fmoc是一种常用的氨基保护基,传统的脱除方法是通过加入二级胺与之作用来实现。针对方法中存在的成本较高、使用的过量二级胺不易回收以及污染环境等缺点,建立了利用新型无机碱纳米碳酸钾非均相脱除Fmoc保护基的新方法。采用湿法研磨方法,将普通碳酸钾制成粒径为64nm的纳米碳酸钾,以Fmoc保护的L-苯丙氨酸的脱保护反应为Model反应,确定了最佳反应条件:反应溶剂为无水乙醇,Fmoc-L-Phe-OBn与纳米碳酸钾物质的量比为1︰2,反应温度为25℃,高产率得到了相应的游离氨基化合物,进一步研究了新方法的适用范围,对7个Fmoc保护的氨基酸和二肽的底物进行了测试。结果表明,产率均在98%以上,且纳米碳酸钾能够回收再利用,在5次之内的活性几乎没有变化。新方法具有操作简单、成本低、污染小、碳酸钾可回收利用的优点,对多肽的合成及脱保护研究有重要的参考价值。Fmoc is usually used as an amino-protecting group.The traditional removal method is realized by using a secondary amine.However,this method has some shortcomings including high cost,difficult recycle of excess secondary amine and environmental pollution.The paper reports a novel heterogeneous deprotection method of Fmoc group using a new inorganic base,namely,nano-potassium carbonate.Nano-potassium carbonate with average particle size 64 nm is prepared using wet grinding method.The deprotection of Fmoc-Phe-OBn is preformed as a Model reaction.The optimum conditions are that reaction solvent is absolute ethanol,molar ratio of Fmoc-L-Phe-OBn to nano-K2CO3 is 1︰2,and reaction temperature is 25 ℃.The corresponding free amino compound is obtained with high yield.To further explore the scope and limitations of this method,seven substrates including Fmoc-anmino acids and dipeptides are examined.All the yields are above 98%.The nano-K2CO3 could beregenarated and reused for 5 times without loss of its reactive activity.This method has the advantages of simple operation,low cost,small pollution and recyclable potassium carbonate,and has important reference value for the research on the synthesis and deprotection of polypeptides.

关 键 词：有机合成化学 纳米碳酸钾 FMOC 脱保护 氨基酸 肽 

分 类 号：O621[理学—有机化学]